Risk factors for cancer from agricultural chemicals in the ambient environment are studied to estimate the contribution of these environmental exposures to cancer in the rural population. Rural populations in agricultural areas have exposures to pesticides and nitrates in drinking water that are intermediate between occupationally-exposed groups and the general population. Case-control studies have been conducted on non-Hodgkin's lymphoma and cancers of the brain, bladder, colon, rectum, stomach, esophagus, pancreas, and kidney. Databases of water contaminants, gathered for routine monitoring purposes, are being used to estimate past exposures via public water supplies to individuals in these case-control studies. Nitrate levels in public water supplies in Iowa were not associated with risk of bladder and pancreas cancer. However, higher intakes of dietary nitrite were associated with an increased risk of pancreas cancer. Overall, drinking water nitrate levels were not associated with risk of colon, rectal, and kidney cancer; however, specific subgroups with increased nitrosation ability were at increased risk of colon and kidney cancer. Among those with higher water nitrate intake and higher red meat intake or lower vitamin C intake, ORs were elevated about two-fold for both colon and kidney cancers. Elevated nitrate in public water supplies in Nebraska was not associated with risk of glioma. Elevated nitrate levels in public drinking water supplies were associated with an increased risk of non-Hodgkin's lymphoma in Nebraska. This hypothesis was investigated in a recently completed case-control investigation of non-Hodgkin's lymphoma in four centers: Iowa, Seattle, Los Angeles and the Detroit area. Nitrate monitoring data for public supplies was linked to water source histories from 1960 onwards. Private wells at interview homes were measured for nitrate. We limited most analyses to those with nitrate estimates for >70% of their person-years since 1960 (181 cases, 142 controls). We found no overall association with the highest quartile of average drinking water nitrate (>2.90 mg/L nitrate-N: OR=1.2, 95% CI 0.6-2.2) or with years >5mg/L (10+ years: OR=1.4, 95% CI 0.7-2.9). We saw no evidence of an interaction between drinking water nitrate exposure and either vitamin C intake or red meat intake, an inhibitor and precursor, respectively, of in vivo NOC formation. Dietary nitrate was inversely associated with risk of NHL (highest quartile OR=0.54, 95% CI 0.34-0.86). Dietary nitrite intake was associated with increasing risk (highest quartile OR=3.1, 95% CI 1.7-5.5), largely due to intakes of bread and cereal sources of nitrite. The issue of nitrate as a cancer risk factor is being pursued further in an ecologic study of census-block groups in the Platte River Valley of Nebraska and Colorado, where elevated nitrate levels are among the highest in the country. Nitrate levels in private wells are being estimated using data on land cover, livestock feedlot locations, soil type, and other information. We are also developing new approaches, and improving existing methods, of exposure assessment in studies of general environmental exposures, with a primary focus on pesticides and nitrate. These better methods are required to better estimate risk and to detect the relatively small increases in risk often encountered in such studies. Geographic information systems (GIS) are being utilized for developing new approaches to estimating indirect exposure to pesticides and for estimating exposure to nitrate in private wells. Remote sensing data (satellite imagery) and historical records were used to estimate the population in Nebraska and Iowa potentially exposed to agricultural pesticides through the proximity of their homes to agricultural land treated with pesticides.